Device and methods for renal nerve modulation monitoring

ABSTRACT

Systems and methods for monitoring and performing tissue modulation are disclosed. An example system may include an elongate shaft having a distal end region and a proximal end and having at least one modulation element and one sensing electrode disposed adjacent to the distal end region. The sensing electrode may be used to determine and monitor changes in tissue adjacent to the modulation element.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §119 to U.S.Provisional Application Ser. No. 61/560,026, filed Nov. 15, 2011, theentirety of which is incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to methods and apparatuses for nervemodulation techniques such as ablation of nerve tissue or otherdestructive modulation technique through the walls of blood vessels andmonitoring thereof.

BACKGROUND

Certain treatments require the temporary or permanent interruption ormodification of select nerve function. One example treatment is renalnerve ablation which is sometimes used to treat hypertension and otherconditions related to hypertension and congestive heart failure. Thekidneys produce a sympathetic response to congestive heart failure,which, among other effects, increases the undesired retention of waterand/or sodium. Ablating some of the nerves running to the kidneys mayreduce or eliminate this sympathetic function, which may provide acorresponding reduction in the associated undesired symptoms.

Many nerves (and nervous tissue such as brain tissue), including renalnerves, run along the walls of or in close proximity to blood vesselsand thus can be accessed intravascularly through the walls of the bloodvessels. In some instances, it may be desirable to ablate perivascularrenal nerves using a radio frequency (RF) electrode in an off-wallconfiguration. However, the electrode and/or temperature sensorsassociated with the device may not be able to detect tissue changes inthe target region because the electrode is not in contact with the wall.Sensing electrodes may allow the use of impedance measuring to monitortissue changes. It is therefore desirable to provide for alternativesystems and methods for intravascular nerve modulation.

SUMMARY

The disclosure is directed to several alternative designs, materials andmethods of manufacturing medical device structures and assemblies forperforming and monitoring tissue changes.

Accordingly, one illustrative embodiment is a system for nervemodulation that may include an elongate shaft having a proximal endregion and a distal end region. An ablation electrode and a firstsensing electrode may be disposed on the elongate shaft adjacent todistal end region. The system may further include a ground pad. Theablation electrode, sensing electrode, and ground pad may beelectrically connected to a control unit.

Another illustrative embodiment is a method for detecting tissue changesduring tissue modulation. A tissue modulation system including anelongate shaft having a proximal end region and a distal end region maybe provided. The modulation system may further include a first electrodedisposed adjacent the distal end region and a second electrode disposedadjacent to the distal end region and spaced a distance from the firstelectrode. The modulation system may be advanced through a lumen suchthat the distal end region is adjacent to a target region. Voltage maybe applied to the modulation system to impart a current between thefirst and second electrodes and an impedance of the target region may becalculated from the current. Voltage may be applied to at least one ofthe first or second electrodes to effect tissue modulation on the targetregion. The current between the first and second electrodes may bemonitored for changes in the impedance of the target region.

The above summary of some example embodiments is not intended todescribe each disclosed embodiment or every implementation of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be more completely understood in consideration of thefollowing detailed description of various embodiments in connection withthe accompanying drawings, in which:

FIG. 1 is a schematic view illustrating a renal nerve modulation systemin situ.

FIG. 2 illustrates a distal end of an illustrative renal nervemodulation system.

FIG. 3 illustrates a distal end of another illustrative renal nervemodulation system.

FIG. 4 illustrates a distal end of another illustrative renal nervemodulation system.

FIG. 5 illustrates a distal end of another illustrative renal nervemodulation system.

FIG. 6 is another illustrative view of the renal nerve modulation systemof FIG. 5.

FIG. 7 illustrates a distal end of another illustrative renal nervemodulation system.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail. It should be understood,however, that the intention is not to limit aspects of the invention tothe particular embodiments described. On the contrary, the intention isto cover all modifications, equivalents, and alternatives falling withinthe spirit and scope of the invention.

DETAILED DESCRIPTION

For the following defined terms, these definitions shall be applied,unless a different definition is given in the claims or elsewhere inthis specification.

All numeric values are herein assumed to be modified by the term“about”, whether or not explicitly indicated. The term “about” generallyrefers to a range of numbers that one of skill in the art would considerequivalent to the recited value (i.e., having the same function orresult). In many instances, the term “about” may be indicative asincluding numbers that are rounded to the nearest significant figure.

The recitation of numerical ranges by endpoints includes all numberswithin that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4,and 5).

Although some suitable dimensions, ranges and/or values pertaining tovarious components, features and/or specifications are disclosed, one ofskill in the art, incited by the present disclosure, would understanddesired dimensions, ranges and/or values may deviate from thoseexpressly disclosed.

As used in this specification and the appended claims, the singularforms “a”, “an”, and “the” include plural referents unless the contentclearly dictates otherwise. As used in this specification and theappended claims, the term “or” is generally employed in its senseincluding “and/or” unless the content clearly dictates otherwise.

The following detailed description should be read with reference to thedrawings in which similar elements in different drawings are numberedthe same. The detailed description and the drawings, which are notnecessarily to scale, depict illustrative embodiments and are notintended to limit the scope of the invention. The illustrativeembodiments depicted are intended only as exemplary. Selected featuresof any illustrative embodiment may be incorporated into an additionalembodiment unless clearly stated to the contrary.

While the devices and methods described herein are discussed relative torenal nerve modulation, it is contemplated that the devices and methodsmay be used in other applications where nerve modulation and/or ablationare desired. For example, the devices and methods described herein mayalso be used for prostate ablation, tumor ablation, and/or othertherapies requiring heating or ablation of target tissue. In someinstances, it may be desirable to ablate perivascular renal nerves withdeep target tissue heating. As energy passes from a modulation elementto the desired treatment region the energy may heat both the tissue andthe intervening fluid (e.g. blood) as it passes. As more energy is used,higher temperatures in the desired treatment region may be achieved thusresulting in a deeper lesion. Monitoring tissue properties may, forexample, verify effective ablation, improve safety, and optimizetreatment time.

In some instances, ablation is performed with the modulation element indirect contact with the vessel or chamber wall. The modulation elementmay contain a thermistor or thermocouple which facilitates monitoring ofthe ablation progress by providing a real-time temperature signal.However, in some instances, it may be advantageous to move themodulation element away from the vessel wall in an off-the-wallconfiguration, such as when circumferential ablation is desired. Duringcircumferential ablation, the modulation element may be positioned atthe center of the lumen. However, when the modulation element does notcontact the vessel wall it may be difficult to detect tissue changesduring and/or after the ablation process. When provided in anoff-the-wall configuration, the modulation element, and thus anytemperature sensing means provided on or adjacent to the ablationelectrode, may be cooled by the blood flow surrounding the modulationelement. As such, thermal feedback may not be useful to providemonitoring as the ablation is performed, resulting in a “blind” ablationscenario. Although the ability to monitor the tissue properties duringcircumferential ablation may be reduced or require additional sensingelements, off-the-wall ablation may allow for free flow of blood acrossthe vessel surface minimizing heat damage to the vessel wall due to theablation process.

In some instances, impedance monitoring may be used to detect changes intarget tissues as ablation progresses. Sensing electrodes may beprovided in addition to the modulation element. In some instances, theimpedance may not be directly measured, but may be a function of thecurrent distribution between the sensing electrodes. In general, theresistance of the surrounding tissue may decrease as the temperature ofthe tissue increases until a point where the tissue begins to denatureor irreversibly change, for example, at approximately 50-60° C. Once thetissue has begun to denature the resistance of the tissue may increase.As the target tissue is ablated, the change in impedance may be analyzedto determine how much tissue has been ablated. The power level andduration of the ablation may be adjusted accordingly based on theimpedance of the tissue.

FIG. 1 is a schematic view of an illustrative renal nerve modulationsystem 10 in situ. System 10 may include an element 12 for providingpower to a nerve modulation element disposed about and/or within acentral elongate shaft 14 and, optionally, within a sheath or guidecatheter 16. A proximal end of element 12 may be connected to a controland power element 18, which supplies the necessary electrical energy toactivate the one or more modulation elements at or near a distal end ofthe element 12. In some instances, return electrode patches 20 may besupplied on the legs or at another conventional location on thepatient's body to complete the circuit. The control and power element 18may include monitoring elements to monitor parameters such as power,temperature, voltage, pulse size, and/or shape and other suitableparameters as well as suitable controls for performing the desiredprocedure. In some instances, the power element 18 may control a radiofrequency (RF) ablation electrode and/or one or more sensing electrodes.It is contemplated that more than one power element 18 may be provided.In some instances, the ablation electrode and the sensing electrode maybe connected to separate power elements 18. The ablation electrode maybe configured to operate at a frequency of approximately 460 kHz. It iscontemplated that any desired frequency in the RF range may be used, forexample, from 100-500 kHz. However, it is contemplated that differenttypes of energy outside the RF spectrum may be used as desired, forexample, but not limited to ultrasound, microwave, and laser to performthe ablation. While the term ablation electrode is used herein, it iscontemplated that the modulation element and modulation frequency may beselected according to the energy used to perform the ablation. Forexample, when ultrasound energy is used, an ultrasonic transducer may beselected as the modulation element and modulation frequencies may be inthe MHz range. The sensing electrodes may be configured to operate overfrequency ranges which are different from the frequency range at whichthe ablation is being performed. It is contemplated that the sensingelectrodes may be operated over a range of frequencies for improvedimpedance measuring.

FIG. 2 is an illustrative embodiment of a distal end of a renal nervemodulation system 100 disposed within a body lumen 102 having a vesselwall 104. The vessel wall 104 may be surrounded by additional bodytissue 106. A portion of the tissue 106 may be the desired treatmentregion 118, 120, as will be discussed in more detail below. The system100 may include an elongate shaft 108 having a distal end region 110.The elongate shaft 108 may extend proximally from the distal end region110 to a proximal end configured to remain outside of a patient's body.The proximal end of the elongate shaft 108 may include a hub attachedthereto for connecting other treatment devices or providing a port forfacilitating other treatments. It is contemplated that the stiffness ofthe elongate shaft 108 may be modified to form a modulation system 100for use in various vessel diameters and various locations within thevascular tree. The elongate shaft 108 may further include one or morelumens extending therethrough. For example, the elongate shaft 108 mayinclude a guidewire lumen and/or one or more auxiliary lumens. Thelumens may be configured in any way known in the art. For example, theguidewire lumen may extend the entire length of the elongate shaft 108such as in an over-the-wire catheter or may extend only along a distalportion of the elongate shaft 108 such as in a single operator exchange(SOE) catheter. These examples are not intended to be limiting, butrather examples of some possible configurations. While not explicitlyshown, the modulation system 100 may further include temperaturesensors/wire, an infusion lumen, radiopaque marker bands, fixedguidewire tip, a guidewire lumen, external sheath and/or othercomponents to facilitate the use and advancement of the system 100within the vasculature.

The system 100 may further include one or more ablation electrodes 112disposed on the outer surface of the elongate shaft 108 adjacent thedistal end region 110. However, the ablation electrode 112 may be placedat any longitudinal location along the elongate shaft desired. While thesystem 100 is illustrated as including one ablation electrode 112, it iscontemplated that the modulation system 100 may include any number ofablation electrodes 112 desired, such as, but not limited to, two,three, four, or more. If multiple ablation electrodes 112 are provided,the ablation electrodes 112 may be longitudinally, radially and/orcircumferentially spaced as desired. In some instances, the ablationelectrode 112 may be a circumferential electrode extending around theouter perimeter of the elongate shaft 108. A circumferential electrode112 may allow for circumferential ablation while reducing and/oreliminating the need for circumferential repositioning of the electrode112 and/or elongate shaft 108. In some embodiments, the ablationelectrode 112 may not extend all the way around the perimeter of theelongate shaft 108. It is contemplated that multiple ablation electrodes112 may be circumferentially positioned around the perimeter of theelongate shaft 108 to reduce and/or eliminate the need tocircumferentially reposition the elongate shaft 108 to perform 360°ablation.

In some embodiments, the ablation electrode 112 may be formed of aseparate structure and attached to the elongate shaft 108. For example,the ablation electrode 112 may be machined or stamped from a monolithicpiece of material and subsequently bonded or otherwise attached to theelongate shaft 108. In other embodiments, the ablation electrode 112 maybe formed directly on the surface of the elongate shaft 108. Forexample, the ablation electrode 112 may be plated, printed, or otherwisedeposited on the surface. In some instances, the ablation electrode 112may sufficiently radiopaque so that it also functions as a radiopaquemarker. The ablation electrode 112 may be formed from any suitablematerial such as, but not limited to, platinum, gold, stainless steel,cobalt alloys, or other non-oxidizing materials. In some instances,titanium, tantalum, or tungsten may be used. It is contemplated that theablation electrode 112 may take any shape desired, such as, but notlimited to, square, rectangular, circular, elliptical, etc. In someembodiments, the ablation electrode 112 may have rounded edges in orderto reduce the affects of sharp edges on current density. The size of theablation electrode 112 may be chosen to optimize the current densitywithout increasing the profile of the modulation system 100. Forexample, an ablation electrode 112 that is too small may generate highlocal current densities resulting in greater heat transfer to the bloodand surrounding tissues. An ablation electrode 112 that is too large mayrequire a larger elongate shaft 108 to carry it. In some instances, theablation electrode 112 may have an aspect ratio of 2:1 (length to width)or greater. Such an elongated structure may provide the ablationelectrode 112 with more surface area without increasing the profile ofthe modulation system 100.

During the ablation procedure, the ablation electrode 112 may bepositioned away from the vessel wall 104 in an off-the-wallconfiguration. While not explicitly shown, modulation system 100 mayfurther include structure to maintain the ablation electrode 112 in theoff-the-wall configuration. For example, in some instances, the elongateshaft may further include a positioning basket configured to expand andengage the vessel wall 104 to center the electrode 112. In otherembodiments, elongate shaft 108 may further include a partiallyocclusive balloon which may be used to position the ablation electrode112 and/or to increase the blood velocity near the ablation electrode112 to provide better vessel wall 104 cooling. It is furthercontemplated that the ablation electrode 112 and/or sensing electrodes114, 116 may be positioned on a positioning basket and/or balloon.

The modulation system 100 may further include a proximal sensingelectrode 114 and a distal sensing electrode 116. The proximal sensingelectrode 114 may be located proximal of the ablation electrode 112 andthe distal sensing electrode 116 may be located distal of the ablationelectrode 112. In some embodiments, the distal sensing electrode 116 maybe located proximal of the distal end 124 of the elongate shaft 108. Inother embodiments, the distal sensing electrode 116 may be adjacent tothe distal end 124 of the elongate shaft 108. While the system isillustrated as including two sensing electrodes 114, 116, it iscontemplated that fewer than or more than two sensing electrodes 114,116 may be provided to improve or provide additional impedanceinformation. In some embodiments, the sensing electrodes may behigh-impedance sensing electrodes. This may minimize the fielddistortion during the measurement. However, in some instances,low-impedance sensing electrodes may be used.

The sensing electrodes 114, 116 may be used to monitor the impedance ofthe tissue separating them. Impedance sensing current 122 may passbetween the proximal 114 and distal 116 sensing electrodes. For clarity,not all of the potential current paths 122 have been illustrated ornumbered. For example, it is contemplated that some current may passthrough the bloodstream between the sensing electrodes 114, 116. Asablation of the target region 118, 120 progresses, the impedanceproperties of the surrounding tissue 118, 120 may change thus changingthe impedance calculated between the proximal sensing electrode 114 andthe distal sensing electrode 116. The sensing electrodes 114, 116 may besymmetrically placed about the ablation electrode 112 such that they caneasily track the change which occurs to the tissue impedance in theablation zone 118, 120 located between them. This may provide improvedsignal-to-noise ratio for better real-time monitoring of the ablationprogress. However, the sensing electrodes 114, 116 may be arranged inany orientation desired and need not be symmetrical about the ablationelectrode 112. While the sensing electrodes 114, 116 are illustrated ina non-contact ablation system 100 it is contemplated that the sensingelectrodes 114, 116 may be used in systems where the ablation electrode112 contacts the vessel wall 104.

In some embodiments, the sensing electrodes 114, 116 may be formed of aseparate structure and attached to the elongate shaft 108. For example,the sensing electrodes 114, 116 may be machined or stamped from amonolithic piece of material and subsequently bonded or otherwiseattached to the elongate shaft 108. In other embodiments, sensingelectrodes 114, 116 may be formed directly on the surface of theelongate shaft 108. For example, the sensing electrodes 114, 116 may beplated, printed, or otherwise deposited on the surface. In someinstances, the sensing electrodes 114, 116 may also function asradiopaque marker bands. The sensing electrodes 114, 116 may be formedfrom any suitable material such as, but not limited to, platinum, gold,stainless steel, cobalt alloys, or other non-oxidizing materials. Insome instances, titanium, tantalum, or tungsten may be used. It iscontemplated that the sensing electrodes 114, 116 may take any shapedesired, such as, but not limited to, square, rectangular, circular,oblong, etc. The size of the sensing electrodes 114, 116 may be chosento optimize the current density without increasing the profile of themodulation system 100.

While not explicitly shown, the sensing electrodes 114, 116 may beconnected to the control unit (such as control unit 18 in FIG. 1) byelectrical conductors. In some embodiments the sensing electrodes 114,116 may be on a separate electrical circuit from the ablation electrode112 and from each other. The sensing electrodes 114, 116 may be operatedat a different frequency than the ablation electrode 112. For example,the frequency, duty cycle, and shape of the excitation waveform of thesensing electrodes 114, 116 can be adapted to yield an optimizedsignal-to-noise ratio for each of the tissue parameters monitored. Insome instances, the sensing electrodes 114, 116 may be operatedsimultaneously with the ablation electrode 112 to provide real-timefeedback of the ablation progress. In other embodiments, the sensingelectrodes 114, 116 may be operated in an alternating fashion (e.g. anablation/sensing duty cycle) with the ablation electrode 112 such thatthe sensing electrodes 114, 116 and the ablation electrode 112 are notsimultaneously active.

While not explicitly shown, the ablation electrode 112 may be connectedto a control unit (such as control unit 18 in FIG. 1) by electricalconductors. Once the modulation system 100 has been advanced to thetreatment region, energy may be supplied to the ablation electrode 112.The amount of energy delivered to the ablation electrode 112 may bedetermined by the desired treatment as well as the feedback obtainedfrom the sensing electrodes 114, 116. As discussed above, once thetarget tissue 118, 120 has begun to denature the resistance of thetissue may increase. The target region 118 nearest the ablationelectrode 112 may receive more energy than the target region 120positioned further away from the ablation electrode 112 and thus maybegin to denature more quickly. As the target tissue 118, 120 isablated, the change in impedance in the tissue 118, 120 may be analyzedto determine how much tissue has been ablated and/or the degree ofdenaturing. The power level and duration of the ablation may be adjustedaccordingly based on the impedance of the tissue. For example, moreenergy may result in a larger, deeper lesion.

The modulation system 100 may be advanced through the vasculature in anymanner known in the art. For example, system 100 may include a guidewirelumen to allow the system 100 to be advanced over a previously locatedguidewire. In some embodiments, the modulation system 100 may beadvanced, or partially advanced, within a guide sheath such as thesheath 16 shown in FIG. 1. Once the ablation electrode 112 of themodulation system 100 has been placed adjacent to the desired treatmentarea, positioning mechanisms may be deployed, if so provided. While notexplicitly shown, the ablation electrode 112 and the sensing electrodes114, 116 may be connected to a single control unit or to separatecontrol units (such as control unit 18 in FIG. 1) by electricalconductors. Once the modulation system 100 has been advanced to thetreatment region, energy may be supplied to the ablation electrode 112and the sensing electrodes 114, 116. As discussed above, the energy maybe supplied to both the ablation electrode 112 and sensing electrodes114, 116 simultaneously or in an alternating fashion at desired. Theamount of energy delivered to the ablation electrode 112 may bedetermined by the desired treatment as well as the feedback provided bythe sensing electrodes 114, 116.

It is contemplated if an ablation electrode 112 is provided that doesnot extend around the entire circumference of the elongate shaft 108,the elongate shaft 108 may need to be circumferentially repositioned andenergy may once again be delivered to the ablation electrode 112 and thesensing electrodes 114, 116 to adequately ablate the target tissue. Thenumber of times the elongate shaft 108 is rotated at a givenlongitudinal location may be determined by the number and size of theablation electrode(s) 112 on the elongate shaft 108. Once a particularlocation has been ablated, it may be desirable to perform furtherablation procedures at different longitudinal locations. Once theelongate shaft 108 has been longitudinally repositioned, energy may onceagain be delivered to the ablation electrode 112, and the sensingelectrodes 114, 116. If necessary, the elongate shaft 108 may becircumferentially repositioned at each longitudinal location. Thisprocess may be repeated at any number of longitudinal locations desired.It is contemplated that in some embodiments, the system 100 may includeablation electrodes 112 at various positions along the length of themodulation system 100 such that a larger region may be treated withoutlongitudinal displacement of the elongate shaft 108.

While FIG. 2 illustrates the sensing electrodes 114, 116 in anoff-the-wall configuration, is contemplated that one or both of thesensing electrodes 114, 116 may be placed in direct contact with thevessel wall 104. As the sensing electrodes 114, 116 may be operated at afrequency and amplitude which does not result in tissue ablation,placing the sensing electrodes 114, 116 against the vessel wall 104 willnot cause the vessel damage. In instances where direct contact ablationis acceptable, the ablation electrode 112 may also be placed in contactwith the vessel wall 104. It is contemplated that the elongate shaft 108may further include an infusion lumen configured to perfuse the vessellumen 102 with saline or other conductive fluid during the ablationprocedure. In some instances, the perfused fluid may be provided at roomtemperature or cooler.

FIG. 3 is an illustrative embodiment of a distal end of a renal nervemodulation system 200 that may be similar in form and function to othersystems disclosed herein. The modulation system may be disposed within abody lumen 202 having a vessel wall 204. The vessel wall 204 may besurrounded by additional body tissues 206 a-f. There may be severaldifferent tissue types 206 a-f surrounding the vessel wall 204. Forexample, the tissues 206 a-f may comprise adventitia and connectivetissues, nerves, fat, fluid, etc. in addition to the muscular vesselwall 204. It is contemplated that some of the body tissues 206 a-f maybe the same type of tissue or may be all different types of tissue. Thebody tissues 206 a-f shown in FIG. 3 is not intended to fully representthe tissue composition surrounding a vessel wall 204, but ratherillustrate that different tissue types and sizes may surround the vesselwall 204. It is to be further understood that while FIG. 3 illustratedthe body tissues 206 a-f on a single side of the vessel wall, the bodytissues 206 a-f may surround the perimeter of the vessel wall 204 and isnot limited to one side.

Each of the different types of tissue 206 a-f may have differentelectrical properties (e.g. impedance, permittivity, conductivity, etc.)and may also have different changes in those properties due to thermalablation. Variation in local tissue types 206 a-f and impedance maycause unpredictable variation in the ablation effect on the targettissue and in local artery wall heating. It may be desirable tocharacterize local tissues and monitor tissue changes in order tocontrol the energy delivery for proper target tissue ablation. The nervemodulation system 200 may include two or more sensing electrodes 214,216 to determine one or more impedance values over a range offrequencies. It is contemplated that tissue impedance may be monitoredduring RF, ultrasound, laser, microwave, or other ablation. Thefrequency at which the sensing electrodes 214, 216 are operated may bechosen according to the tissue material present or expected to bepresent. The impedance may be used to evaluate which type(s) of tissueare adjacent to the ablation region and to monitor changes which occurby thermal ablation of that tissue(s).

The system 200 may include an elongate shaft 208 having a distal endregion 210 and a distal end 220. The elongate shaft 208 may extendproximally from the distal end 220 to a proximal end configured toremain outside of a patient's body. The proximal end of the elongateshaft 208 may include a hub attached thereto for connecting othertreatment devices or providing a port for facilitating other treatments.It is contemplated that the stiffness of the elongate shaft 208 may bemodified to form modulation system 200 for use in various vesseldiameters. The elongate shaft 208 may further include one or more lumensextending therethrough. For example, the elongate shaft 208 may includea guide wire lumen and/or one or more auxiliary lumens. The lumens maybe configured in any suitable way such as those ways commonly used formedical devices. While not explicitly shown, the modulation system 200may further include temperature sensors/wire, an infusion lumen,radiopaque marker bands, fixed guidewire tip, external sheath and/orother components to facilitate the use and advancement of the system 200within the vasculature.

The system 200 may further include one or more ablation electrodes 212disposed on the outer surface of the elongate shaft 208. While thesystem 200 is illustrated as including a single ablation electrode 212,it is contemplated that the modulation system 200 may include any numberof ablation electrodes 212 desired, such as, but not limited to, two,three, four, or more. If multiple ablation electrodes 212 are provided,the ablation electrodes 212 may be longitudinally and/or radially spacedas desired. The ablation electrode 212 may include similar features andmay function in a similar manner to the ablation electrode discussedwith respect to FIG. 2.

During the ablation procedure, the ablation electrode 212 may bepositioned away from the vessel wall 204 in an off-the-wallconfiguration. While not explicitly shown, the modulation system 200 mayfurther include structure to maintain the ablation electrode 212 in theoff-the-wall configuration. For example, in some instances the elongateshaft may further include a positioning basket configured to expand andengage the vessel wall 204 to center the electrode 212. In otherembodiments elongate shaft 208 may further include a partially occlusiveballoon which may be used to position the ablation electrode 212 and/orto increase the blood velocity near the ablation electrode 212 toprovide better vessel wall cooling. It is further contemplated that theablation electrode 212 and/or sensing electrodes 214, 216 may bepositioned on a positioning basket and/or balloon.

The modulation system 200 may further include a proximal sensingelectrode 214 and a distal sensing electrode 216. It is contemplatedthat the modulation system 200 may include more than two sensingelectrodes 214, 216 to further refine the tissue evaluation. The sensingelectrodes 214, 216 may include similar features and may function in asimilar manner to the sensing electrodes discussed with respect to FIG.2. In some instances, high impedance sensing electrodes 214, 216 may beused in order to avoid significant distortion of the electric field andto avoid bipolar ablation between the ablation electrode 212 and thesensing electrodes 214, 216. The proximal sensing electrode 214 may belocated proximal of the ablation electrode 212 and the distal sensingelectrode 216 may be located distal of the ablation electrode 212. Insome embodiments, the distal sensing electrode 216 may be locatedadjacent to the distal end 220 of the elongate shaft 208. In otherembodiments, the distal sensing electrode 216 may be proximal of thedistal end 220 of the elongate shaft 208.

The sensing electrodes 214, 216 may be used to monitor the impedance ofthe tissue separating them. While not explicitly shown, the sensingelectrodes 214, 216 may be connected through separate insulatedconductors to a control unit (such as control unit 18 illustrated inFIG. 1). In some embodiments the sensing electrodes 214, 216 may be on aseparate electrical circuit from the ablation electrode 212. The sensingelectrodes 214, 216 may be operated at a different frequency than theablation electrode 212. For example, the frequency, duty cycle, andshape of the excitation waveform of the sensing electrodes 214, 216 canbe adapted to yield an optimized signal-to-noise ratio for each of thetissue parameters monitored. When voltage is applied across the sensingelectrodes 214, 216, a small current 218 may flow through the tissues206 a-f. For clarity, not all of the potential current paths 218 havebeen illustrated or numbered. For example, it is contemplated that somecurrent may pass through the bloodstream in lumen 202. The current 218may be monitored by the control unit and used to determine the localtissue impedance in the vicinity of the sensing electrodes 214, 216.Various frequencies may be used to determine one or more impedancevalues, or a simpler calculation of resistance at low frequently can beutilized. Tissue impedance may vary at different temperatures and mayalso be affected by protein changes, perfusion changes, and fluidchanges as a result of thermal ablation. The different tissues havedifferent electrical properties and also react differently to thermalablation. The impedance measurements may be used to determine whichtissues are in the local ablation region, and to monitor changes whichoccur by ablation of those tissues. The use of various frequencies mayallow for better discrimination between tissue types and monitoring ofablative changes. Accordingly, ongoing impedance monitoring may be usedto evaluate whether the modulation system 200 and positionedappropriately treat target tissue and determine when ablation has beencompleted. It is contemplated that undesired changes, such as ablativechanges to the muscular vessel wall 204, can also be detected.

Tissue impedance may be monitored during simultaneous RF ablation (e.g.energy is applied simultaneously to the ablation electrode 212 and thesensing electrodes 214, 216). In such a case, most of the current mayflow between the ablation electrode 212 and a skin contact ground pad(such as ground contact pad 20 in FIG. 1) and through the perivasculartarget tissues to be ablated, while a small amount of current may flowbetween the ablation electrode 212 and at least one higher impedancesensing electrode 214, 216. In this instance, it is contemplated thatbody impedance between the ablation electrode 212 and skin contactground pad may also be measured. It is further contemplated that tissueimpedance may be monitored during ablation/sensing duty cycle which maybe used alternate between ablation and impedance measurement. Asablation of the target region progresses, the impedance properties ofthe surrounding tissues 206 a-f may change thus changing the impedancecalculated between the proximal sensing electrode 214 and the distalsensing electrode 216, between the ablation electrode 212 and thecontact ground pad, and/or between the ablation electrode 212 and one ormore sensing electrodes 214, 216.

While not explicitly shown, the ablation electrode 212 may be connectedto a control unit (such as control unit 18 in FIG. 1) by electricalconductors. Once the modulation system 200 has been advanced to thetreatment region, energy may be supplied to the ablation electrode 212.The amount of energy delivered to the ablation electrode 212 may bedetermined by the desired treatment as well as the feedback obtainedfrom the sensing electrodes 214, 216. As discussed above, once thetarget tissue has begun to denature the electrical properties of thetissue may begin to change. As the target tissue is ablated, the changein impedance may be analyzed to determine how much tissue has beenablated. The power level and duration of the ablation may be adjustedaccordingly based on the impedance of the tissue. In some instances, themodulation system 200 may monitor impedance values of the surroundingtissues 206 a-f prior to beginning the ablation procedure and adjust theablation parameters accordingly. It is further contemplated that otherelectrical properties of the tissues 206 a-f such as permittivity and/orconductivity may be used to set the current and/or power for RF or otherablation energy to target tissues.

The modulation system 200 may be advanced through the vasculature in anymanner known in the art. For example, system 200 may include a guidewirelumen to allow the system 200 to be advanced over a previously locatedguidewire. In some embodiments, the modulation system 200 may beadvanced, or partially advanced, within a guide sheath such as thesheath 16 shown in FIG. 1. Once the ablation electrode 212 of themodulation system 200 has been placed adjacent to the desired treatmentarea, positioning mechanisms may be deployed, if so provided. While notexplicitly shown, the ablation electrode 212 and the sensing electrodes214, 216 may be connected to a single control unit or to separatecontrol units (such as control unit 18 in FIG. 1) by electricalconductors. Once the modulation system 200 has been advanced to thetreatment region, energy may be supplied to the ablation electrode 212and the sensing electrodes 214, 216. As discussed above, the energy maybe supplied to both the ablation electrode 212 in sensing electrodes214, 216 simultaneously or in an alternating duty cycle at desired. Theamount of energy delivered to the ablation electrode 212 may bedetermined by the desired treatment as well as the feedback provided bythe sensing electrodes 214, 216.

It is contemplated if an ablation electrode 212 is provided that doesnot extend around the entire circumference of the elongate shaft 208,the elongate shaft 208 may need to be circumferentially repositioned andenergy may once again be delivered to the ablation electrode 212 and thesensing electrodes 214, 216 to adequately ablate the target tissueablation. The number of times the elongate shaft 208 is rotated at agiven longitudinal location may be determined by the number and size ofthe ablation electrode(s) 212 on the elongate shaft 208. Once aparticular location has been ablated, it may be desirable to performfurther ablation at different longitudinal locations. Once the elongateshaft 208 has been longitudinally repositioned, energy may once again bedelivered to the ablation electrode 212, and the sensing electrodes 214,216. If necessary, the elongate shaft 208 may be circumferentiallyrepositioned at each longitudinal location. This process may be repeatedat any number of longitudinal locations desired. It is contemplated thatin some embodiments, the system 200 may include ablation electrodes 212at various positions along the length of the modulation system 200 suchthat a larger region may be treated without longitudinal displacement ofthe elongate shaft 208.

While FIG. 3 illustrates the sensing electrodes 214, 216 in anoff-the-wall configuration, it is contemplated that one or both of thesensing electrodes 214, 216 may be placed in direct contact with thevessel wall 204. As the sensing electrodes 214, 216 may be operated at afrequency and amplitude which does not result in tissue ablation,placing the sensing electrodes 214, 216 against the vessel wall 204 willnot cause the vessel damage. In instances where direct contact ablationis acceptable, the ablation electrode 212 may also be placed in contactwith the vessel wall 204. It is contemplated that the elongate shaft 208may further include an infusion lumen configured to perfuse the vessellumen 202 with saline or other conductive fluid during the ablationprocedure. In some instances, the perfused fluid may be provided at roomtemperature or cooler.

FIG. 4 is an illustrative embodiment of a distal end of a renal nervemodulation system 300 that may be similar in form and function to othersystems disclosed herein. The modulation system 300 may be disposedwithin a body lumen 302 having a vessel wall 304. The vessel wall 304may be surrounded by local target tissue 306. It may be desirable todetermine local tissue impedance and monitor tissue changes in order tocontrol the energy delivery for proper target tissue ablation. The nervemodulation system 300 may include a high-impedance sensing electrode 314to determine local impedance. It is contemplated that tissue impedancemay be monitored during RF, ultrasound, laser, microwave, or otherablation methods.

The system 300 may include an elongate shaft 308 having a distal end310. The elongate shaft 308 may extend proximally from the distal end310 to a proximal end configured to remain outside of a patient's body.The proximal end of the elongate shaft 308 may include a hub attachedthereto for connecting other treatment devices or providing a port forfacilitating other treatments. It is contemplated that the stiffness ofthe elongate shaft 308 may be modified to form modulation system 300 foruse in various vessel diameters. The elongate shaft 308 may furtherinclude one or more lumens extending therethrough. For example, theelongate shaft 308 may include a guide wire lumen and/or one or moreauxiliary lumens. The lumens may be configured in any suitable way suchas those ways commonly used for medical devices. While not explicitlyshown, the modulation system 300 may further include temperaturesensors/wires, an infusion lumen, radiopaque marker bands, fixedguidewire tip, external sheath and/or other components to facilitate theuse and advancement of the system 300 within the vasculature.

The system 300 may further include one or more ablation electrodes 312disposed on the outer surface of the elongate shaft 308. While thesystem 300 is illustrated as including one ablation electrode 312, it iscontemplated that the modulation system 300 may include any number ofablation electrodes 312 desired, such as, but not limited to, two,three, four, or more. If multiple ablation electrodes 312 are provided,the ablation electrodes 312 may be longitudinally and/or radially and/orcircumferentially spaced as desired. The ablation electrode 312 mayinclude similar features and may function in a similar manner to theablation electrode discussed with respect to FIG. 2. In someembodiments, the ablation electrode 312 may be positioned adjacent tothe distal end 310 of the elongate shaft 308. In other embodiments, theablation electrode 312 may be positioned proximal of the distal end 310.

The modulation system 300 may further include a sensing electrode 314.It is contemplated that the modulation system 300 may include more thanone sensing electrode 314 to further refine the tissue evaluation. Thesensing electrode 314 may include similar features and may function in asimilar manner to the sensing electrode discussed with respect FIG. 2.In some instances, a high impedance sensing electrode 314 may be used inorder to avoid significant distortion of the electric field and to avoidbipolar ablation between the ablation electrode 312 and the sensingelectrode 314. In some embodiments, the sensing electrode 314 may belocated proximal of the ablation electrode 312. In other embodiments,the sensing electrode 314 may be located distal of the ablationelectrode 312.

The ablation electrode 312 and the sensing electrode 314 may be used tomonitor the impedance of the local tissue 306. While not explicitlyshown, the ablation electrode 312 and the sensing electrode 314 may beconnected through separate insulated conductors to a control unit (suchas control unit 18 in FIG. 1). A skin-contact ground pad 320 may also beconnected through an electrical conductor 324 to the control unit. Asvoltage is applied to the ablation electrode 312, current 322 may passthrough the local tissue 306 and additional body tissue 318 to theground pad 320. During ablation, the sensing electrode 314 may be usedas a reference electrode and measure the local voltage at a knownlocation in the local tissue 306, which may be monitored by the controlunit. The local voltage may be used to determine the local tissueimpedance between the ablation electrode 312 and the sensing electrode314. Various frequencies may be used to determine one or more impedancevalues, or a simpler calculation of resistance at low frequency can beutilized.

Tissue impedance may be monitored during simultaneous RF ablation (e.g.energy is applied simultaneously to the ablation electrode 312 and thesensing electrodes 314). In such a case, most of the current 322 mayflow between the ablation electrode 312 and the skin-contact ground pad320 and through the perivascular target tissues to be ablated, while asmall amount of current 316 may flow between the ablation electrode 312and the high impedance sensing electrode 314. In this instance, the bodyimpedance resulting from body tissue 318 outside of the target tissueregion 306 between the ablation electrode 312 and skin contact groundpad 320 may also be measured. Tissue distribution and make-up may varyfrom patient to patient. For example, in some instances, a large portionof the power applied to the system 300 (e.g. approximately 80% in somecases) may be distributed locally, or within approximately two to threeradii of the ablation electrode 312, while the remaining portion (e.g.approximately 20%) is distributed throughout the remainder of the body(e.g across the skin, subcutaneous fat, and/or other tissue not in thelocal target tissue 306). As the body composition may vary from personto person, the power distribution may also vary. The modulation system300 may be configured to normalize the voltage supplied to the ablationelectrode 312 to account for variations in impedance of the patient'sbody. It is contemplated that the local voltage (e.g. the differencebetween the voltage at the ablation electrode 312 and the voltage at thesensing electrode 314) may be used to determine the local power density(e.g. the power density adjacent to the ablation electrode 312). Forexample, the local power density may be determined by the Equation 1:P_(loc)=IΔV  (1)where P_(loc) is the local power density, I is the current, and ΔV isthe difference between the voltage at the ablation electrode 312 and thevoltage at the sensing electrode 314. The local power density may thenbe used to adjust the power delivery of the system 300 to achieve thedesired tissue modulation.

It is further contemplated that tissue impedance may be monitored duringan ablation/sensing duty cycle which may be used alternate betweenablation and impedance measurements. As ablation of the target regionprogresses, the impedance properties of the local tissue 306 may changethus changing the impedance calculated between the ablation electrode312 and the contact ground pad 320 and/or between the ablation electrode312 and the sensing electrode 314. It is contemplated that poor groundpad 320 contact may also be detected during the ablation process.

While not explicitly shown, the ablation electrode 312 may be connectedto a control unit (such as control unit 18 in FIG. 1) by electricalconductors. Once the modulation system 300 has been advanced to thetreatment region, energy may be supplied to the ablation electrode 312.The amount of energy delivered to the ablation electrode 312 may bedetermined by the desired treatment as well as the feedback obtainedfrom the sensing electrodes 314. Once the target tissue has begun torise in temperature, and/or denature, the electrical properties of thetissue may begin to change. As the target tissue is ablated, the changein impedance may be analyzed to determine how much tissue has beenablated. The power level and duration of the ablation may be adjustedaccordingly based on the impedance of the tissue. In some instances, themodulation system 300 may monitor impedance values of the surroundingtissue 306 prior to beginning the ablation procedure and adjust theablation parameters accordingly. It is further contemplated that otherelectrical properties of the local tissue 306 such as permittivityand/or conductivity may be used to set the current and/or power for RFor other sources of ablation energy to target tissues.

The modulation system 300 may be advanced through the vasculature in anymanner known in the art. For example, system 300 may include a guidewirelumen to allow the system 300 to be advanced over a previously locatedguidewire. In some embodiments, the modulation system 300 may beadvanced, or partially advanced, within a guide sheath such as thesheath 16 shown in FIG. 1. Once the ablation electrode 312 of themodulation system 300 has been placed adjacent to the desired treatmentarea, positioning mechanisms may be deployed, if so provided. Forexample, in some embodiments, the elongate shaft 308 may include pushand/or pull wires to deflect a distal end region of the elongate shaft308. For example, a push and/or pull wire may be attached adjacent tothe distal end 310 of the elongate shaft 308 and then extend along anouter surface of the elongate shaft 308 or along an interior passagewayformed in the shaft 308 to a position where it is accessible to a user.In other embodiments, the elongate shaft 308 may incorporate a planardeflection mechanism, such as a rib and spine mechanism. However, it iscontemplated that the elongate shaft 308 may be deflected in any desiredmanner. The ablation electrode 312 and the sensing electrode 314 may bepositioned adjacent to the deflectable region of the elongate shaft 308.Deflection of the elongate shaft 308 may position the ablation electrode312 adjacent a first target region and the sensing electrode 314adjacent a second target region.

As discussed above, the ablation electrode 312 and the sensing electrode314 may be connected to a control unit (such as control unit 18 inFIG. 1) by insulated electrical conductors. Once the modulation system300 has been advanced to the treatment region, energy may be supplied tothe ablation electrode 312. As discussed above, the energy may besupplied to both the ablation electrode 312 and/or the sensing electrode314 simultaneously or in an alternating duty cycle as desired. Theamount of energy delivered to the ablation electrode 312 may bedetermined by the desired treatment as well as the feedback provided bythe sensing electrode 314.

It is contemplated if an ablation electrode 312 is provided that doesnot extend around the entire circumference of the elongate shaft 308,the elongate shaft 308 may need to be circumferentially repositioned andenergy may once again be delivered to the ablation electrode 312 toadequately ablate the target tissue. The number of times the elongateshaft 308 is rotated at a given longitudinal location may be determinedby the number and size of the ablation electrode(s) 312 on the elongateshaft 308. Once a particular location has been ablated, it may bedesirable to perform further ablation at different longitudinallocations. Once the elongate shaft 308 has been longitudinallyrepositioned, energy may once again be delivered to the ablationelectrode 312. If necessary, the elongate shaft 308 may becircumferentially repositioned at each longitudinal location. Thisprocess may be repeated at any number of longitudinal locations desired.It is contemplated that in some embodiments, the system 300 may includeablation electrodes 312 at various positions along the length of themodulation system 300 such that a larger region may be treated withoutlongitudinal displacement of the elongate shaft 308.

While FIG. 4 illustrates the ablation electrode 312 and the sensingelectrode 314 in direct contact with the vessel wall, it is contemplatedthat the ablation electrode 312 and/or the sensing electrode 314 may bepositioned away from the vessel wall 304 in an off-the-wallconfiguration. While not explicitly shown, the modulation system 300 mayfurther include structure to maintain the ablation electrode 312 in theoff-the-wall configuration. For example, in some instances the elongateshaft may further include a positioning basket configured to expand andengage the vessel wall 304 to center the electrode 312. In otherembodiments elongate shaft 308 may further include a partially occlusiveballoon which may be used to position the ablation electrode 312 and/orto increase the blood velocity near the ablation electrode 312 toprovide better vessel wall cooling. It is contemplated that the elongateshaft 308 may further include an infusion lumen configured to perfusethe vessel lumen 302 with saline or other conductive fluid during theablation procedure. In some instances, the perfused fluid may beprovided at room temperature or cooler.

FIG. 5 is another illustrative embodiment of a distal end of a renalnerve modulation system 400 that may be similar in form and function toother systems disclosed herein. The modulation system 400 may bedisposed within a body lumen 402 having a vessel wall 404. The vesselwall 404 may be surrounded by local target tissue. It may be desirableto determine local tissue impedance and monitor tissue changes in orderto control energy delivery for proper target tissue ablation. The nervemodulation system 400 may include a high-impedance or low-impedancesensing electrode 414 to determine local impedance in the target tissueand surrounding blood. It is contemplated that tissue impedance may bemonitored during RF, ultrasound, laser, microwave, or other ablationmethods.

The system 400 may include an elongate member 406 having an expandableframework 408 disposed adjacent the distal end region 410. In someinstances, the modulation system 400 may include an expandable balloonin place of the expandable framework 408. It is further contemplatedthat the modulation system 400 may not include an expandable portion.The elongate member 406 may extend proximally from the distal end region410 to a proximal end configured to remain outside of a patient's body.The proximal end of the elongate member 406 may include a hub attachedthereto for connecting other treatment devices or providing a port forfacilitating other treatments. It is contemplated that the stiffness ofthe elongate member 406 may be modified to form modulation system 400for use in various vessel diameters. In some instances, the elongatemember 406 may be a wire having a generally solid cross-section. Inother embodiments, the elongate member 406 may include one or morelumens extending therethrough. For example, the elongate member 406 mayinclude a guide wire lumen and/or one or more auxiliary lumens. Thelumens may be configured in any suitable way such as those ways commonlyused for medical devices. While not explicitly shown, the modulationsystem 400 may further include temperature sensors/wires, an infusionlumen, radiopaque marker bands, fixed guidewire tip, external sheathand/or other components to facilitate the use and advancement of thesystem 400 within the vasculature.

The system 400 may further include one or more ablation electrodes 412disposed on the expandable framework 408. The ablation electrodes 412may be positioned on separate struts 432 of the expandable framework 408such that the when the framework 408 is expanded the ablation electrodes412 are positioned adjacent to opposite sides of the vessel wall 404.While the system 400 is illustrated as including two ablation electrodes412, it is contemplated that the modulation system 400 may include anynumber of ablation electrodes 412 desired, such as, but not limited to,one, three, four, or more. If multiple ablation electrodes 412 areprovided, the ablation electrodes 412 may be longitudinally and/orradially and/or circumferentially spaced as desired. In some instances,the ablation electrodes 412 may be positioned to be adjacent to oppositesides of the vessel 404. The ablation electrodes 412 may include similarfeatures and may function in a similar manner to the ablation electrodediscussed with respect to FIG. 2. In some embodiments, the ablationelectrodes 412 may be positioned proximal of the distal end region 410of the elongate member 406. In other embodiments, the ablationelectrodes 412 may be positioned adjacent to the distal end region 410.It is further contemplated that the ablation electrodes 412 may functionas both ablation and sensing electrodes.

The modulation system 400 may further include a sensing electrode 414.It is contemplated that the modulation system 400 may include more thanone sensing electrode 414 to further refine the tissue evaluation. Thesensing electrode 414 may include similar features and may function in asimilar manner to the sensing electrode discussed with respect FIG. 2.In some instances, a high impedance sensing electrode 414 may be used inorder to avoid significant distortion of the electric field and to avoidbipolar ablation between the ablation electrode 412 and the sensingelectrode 414. In other instances, a low-impedance sensing electrode 414may be used. In some embodiments, the sensing electrode 414 may belocated distal of the ablation electrodes 412 and adjacent to the distalend region 410. In other embodiments, the sensing electrode 414 may belocated proximal of the ablation electrodes 412.

The ablation electrodes 412 and the sensing electrode 414 may be used tomonitor the impedance of the local tissue. While not explicitly shown,the ablation electrode 412 and the sensing electrode 414 may beconnected through separate insulated conductors to a control unit (suchas control unit 18 in FIG. 1). In some instances, the ablationelectrodes 412 may be used as sensing electrodes to determine localtissue impedance. The ablation electrodes 412 may be spaced a distancefrom the sensing electrode 414 such that voltage applied to theelectrodes 412, 414 may cause current to flow between the electrodes412, 414 through the blood and nearby tissues. Measurement of thecurrent may allow the resistance or complex impedance of the blood andtissue to be calculated. Various frequencies may be used to determineone or more impedance values, or a simpler calculation of resistance atlow frequency can be utilized.

In some instances, it may be desirable to calculate the impedance of theblood or other fluid within the body lumen 402. The modulation systemmay include a catheter shaft 416 including a lumen for perfusing salineor other fluid 418 with known conductivity into the body lumen 402. Insome instances, the perfused fluid 418 may be provided at roomtemperature or cooler. It is contemplated that multiple fluids and/orconcentrations with known conductivity may be used. The impedance may bedetermined while the fluid 418 is being perfused. The difference betweenthe impedance calculated with blood and the impedance calculated withthe perfused fluid may be used to calculate the impedance of the blood.Referring to FIG. 6, which illustrates the current paths between variouselectrodes and ground pads, skin-contact ground pads 420 may also beconnected through an electrical conductor to the control unit. Asvoltage is applied to the ablation electrodes 412, current 430 may passthrough the local tissue 422 and additional body tissue 428 to theground pads 420. Analysis of the impedance measurements between theablation electrodes 412 and the sensing electrode 414 and between theablation electrodes 412 and the ground pads 420 and/or between thesensing electrode 414 and the ground pads 420 may determine the tissueimpedance in the local tissue 422 (e.g. target region) adjacent theelectrodes 412, 414.

Tissue impedance may be monitored during simultaneous RF ablation (e.g.energy is applied simultaneously to the ablation electrode 412 and thesensing electrodes 414). In such a case, most of the current 430 mayflow between the ablation electrode 412 and the skin-contact ground pads420 and through the perivascular target tissues to be ablated, while asmall amount of current 424, 426 may flow between the ablationelectrodes 412 and the sensing electrode 414. As noted above, some ofthe current 424 will pass through the local tissue 422 while some of thecurrent 426 will pass through the fluid in the body lumen 402 (e.g.blood or perfused fluid). The body impedance resulting from body tissue428 outside of the local tissue 422 region between the ablationelectrode 412 and skin contact ground pad 420 may also be measured. Theimpedance of the blood, local tissue 422, and body tissue 428 may beused to properly adjust the RF energy applied for ablation of the targettissue. It is further contemplated that impedance of the blood, localtissue 422, and body tissue 428 may be monitored during anablation/sensing duty cycle which may be used alternate between ablationand impedance measurements. As ablation of the target region progresses,the impedance properties of the local tissue may change thus changingthe impedance calculated between the ablation electrode 412 and thecontact ground pad 420 and/or between the ablation electrodes 412 andthe sensing electrode 414. Multiple measurements between the electrodes412, 414 and/or the ground pads 420 (with blood or perfused fluid 418)may account for the location of the system 400 and vessel geometryeffects. It is contemplated that poor ground pad 420 contact may also bedetected during the ablation process.

While not explicitly shown, the ablation electrodes 412 may be connectedto a control unit (such as control unit 18 in FIG. 1) by electricalconductors. Once the modulation system 400 has been advanced to thetreatment region, energy may be supplied to the ablation electrodes 412.The amount of energy delivered to the ablation electrodes 412 may bedetermined by the desired treatment as well as the feedback obtainedfrom the impedance calculations. It is contemplated that the impedanceof the blood, local tissue 422, and body tissue 428 may be determinedprior to and/or during the ablation procedure. Once the target tissuehas begun to rise in temperature, and/or denature, the electricalproperties of the tissue may begin to change. As the target tissue isablated, the change in impedance may be analyzed to determine how muchtissue has been ablated. The power level and duration of the ablationmay be adjusted accordingly based on the impedance of the tissue. Insome instances, the modulation system 400 may monitor impedance valuesof the surrounding tissue prior to beginning the ablation procedure andadjust the ablation parameters accordingly. It is further contemplatedthat other electrical properties of the local tissue such aspermittivity and/or conductivity may be used to set the current and/orpower for RF or other sources of ablation energy to target tissues.

The modulation system 400 may be advanced through the vasculature in anymanner known in the art. For example, system 400 may include a guidewirelumen to allow the system 400 to be advanced over a previously locatedguidewire. In some embodiments, the modulation system 400 may beadvanced, or partially advanced, within a guide sheath such as thesheath 16 shown in FIG. 1. Once the ablation electrodes 412 of themodulation system 400 have been placed adjacent to the desired treatmentarea, positioning mechanisms may be deployed, if so provided. Forexample, once the distal end region 410 has been placed adjacent to thetarget region, the catheter shaft 416 may be retracted and the framework408 allowed to expand. It is contemplated that other known mechanismsmay be used to deploy the framework 408. For example, a stent orexpandable balloon may be used to expand the framework 408. It isfurther contemplated that the framework 408 may be formed of ashape-memory material, such as nitinol, such that additional structureis not necessary to expand the framework 408. Expansion of the framework408 may place the ablation electrodes 412 adjacent to the desiredtreatment region.

As discussed above, the ablation electrodes 412 and the sensingelectrode 414 may be connected to a control unit (such as control unit18 in FIG. 1) by insulated electrical conductors. Once the modulationsystem 400 has been advanced to the treatment region, energy may besupplied to the ablation electrodes 412. As discussed above, the energymay be supplied to both the ablation electrodes 412 and/or the sensingelectrode 414 simultaneously or in an alternating duty cycle as desired.The amount of energy delivered to the ablation electrodes 412 may bedetermined by the desired treatment as well as the feedback provided bythe sensing electrode 414.

It is contemplated if an ablation electrode 412 is provided that doesnot extend around the entire circumference of the elongate member 406,the elongate member 406 may need to be circumferentially and/or radiallyrepositioned and energy may once again be delivered to the ablationelectrodes 412 to adequately ablate the target tissue. The number oftimes the elongate member 406 is repositioned at a given longitudinallocation may be determined by the number and size of the ablationelectrodes 412 on the elongate member 406. Once a particular locationhas been ablated, it may be desirable to perform further ablation atdifferent longitudinal locations. Once the elongate member 406 has beenlongitudinally repositioned, energy may once again be delivered to theablation electrodes 412. If necessary, the elongate member 406 may beradially repositioned at each longitudinal location. This process may berepeated at any number of longitudinal locations desired. It iscontemplated that in some embodiments, the system 400 may includeablation electrodes 412 at various positions along the length of themodulation system 400 such that a larger region may be treated withoutlongitudinal displacement of the elongate member 406.

While FIG. 5 illustrates the sensing electrodes 414 in an off-the-wallconfiguration, it is contemplated that the sensing electrodes 414 may bein direct contact with the vessel wall 404. As the sensing electrodes414 may be operated at a frequency which does not result in tissueablation, placing the sensing electrodes 414 against the vessel wall 404will not cause vessel damage. In instances where direct contact ablationis acceptable, the ablation electrodes 412 may also be placed in contactwith the vessel wall 404.

FIG. 7 is another illustrative embodiment of a distal end of a renalnerve modulation system 500 that may be similar in form and function toother systems disclosed herein. The modulation system 500 may bedisposed within a body lumen 502 having a vessel wall 504. The vesselwall 504 may be surrounded by local target tissue. It may be desirableto determine local tissue impedance and monitor tissue changes in orderto control energy delivery for proper target tissue ablation. The nervemodulation system 500 may include one or more high-impedance orlow-impedance sensing electrodes 514, 516 to determine local impedancein the target tissue and surrounding blood. It is contemplated thattissue impedance may be monitored during unipolar or bipolar RF,ultrasound, laser, microwave, or other ablation methods.

The system 500 may include an elongate member 506 having an expandableframework 508 disposed adjacent the distal end region 510 may includesimilar features and may function in a similar manner to the expandableframework described with respect to FIG. 5. The elongate member 506 mayextend proximally from the distal end region 510 to a proximal endconfigured to remain outside of a patient's body. The proximal end ofthe elongate member 506 may include a hub attached thereto forconnecting other treatment devices or providing a port for facilitatingother treatments. It is contemplated that the stiffness of the elongatemember 506 may be modified to form modulation system 500 for use invarious vessel diameters. In some instances, the elongate member 506 maybe a wire having a generally solid cross-section. In other embodiments,the elongate member 506 may include one or more lumens extendingtherethrough. For example, the elongate member 506 may include a guidewire lumen and/or one or more auxiliary lumens. The lumens may beconfigured in any suitable way such as those ways commonly used formedical devices. While not explicitly shown, the modulation system 500may further include temperature sensors/wires, an infusion lumen,radiopaque marker bands, fixed guidewire tip, external sheath and/orother components to facilitate the use and advancement of the system 500within the vasculature.

The system 500 may further include one or more ablation electrodes 512disposed on the expandable framework 508. The ablation electrodes 512may be positioned on separate struts 522 of the expandable framework 508such that the when the framework 508 is expanded the ablation electrodes512 are positioned adjacent to opposite sides of the vessel wall 504.While the system 500 is illustrated as including two ablation electrodes512, it is contemplated that the modulation system 500 may include anynumber of ablation electrodes 512 desired, such as, but not limited to,one, three, four, or more. If multiple ablation electrodes 512 areprovided, the ablation electrodes 512 may be longitudinally and/orradially and/or circumferentially spaced as desired. In some instances,the ablation electrodes 512 may be positioned to be adjacent to oppositesides of the vessel 504. The ablation electrodes 512 may include similarfeatures and may function in a similar manner to the ablation electrodediscussed with respect to FIG. 2. In some embodiments, the ablationelectrodes 512 may be positioned proximal of the distal end region 510of the elongate member 506. In other embodiments, the ablationelectrodes 512 may be positioned adjacent to the distal end region 510.It is further contemplated that the ablation electrodes 512 may functionas both ablation and sensing electrodes.

The modulation system 500 may further include a pair of proximal sensingelectrodes 514 and a pair of distal sensing electrodes 516. It iscontemplated that the modulation system 500 may include fewer than ormore than four sensing electrodes 514, 516 to further refine the tissueevaluation. The sensing electrodes 514, 516 may include similar featuresand may function in a similar manner to the sensing electrodes discussedwith respect FIG. 2. In some instances, high-impedance sensingelectrodes 514, 516 may be used in order to avoid significant distortionof the electric field and to avoid bipolar ablation between the ablationelectrodes 512 and the sensing electrodes 514, 516. In other instances,low-impedance sensing electrodes 514, 516 may be used. The sensingelectrodes 514, 516 may be symmetrically placed about the ablationelectrodes 512 such that they can easily track the change which occursto the tissue impedance in the ablation zone located between them.However, the sensing electrodes 514, 516 may be arranged in anyorientation desired. The sensing electrodes 514, 516 may be in directcontact with the vessel wall 504. As the sensing electrode 414 may beoperated at a frequency which does not result in tissue ablation,placing the sensing electrodes 514, 516 against the vessel wall 504 willnot cause vessel damage. In instances where direct contact ablation isacceptable, the ablation electrodes 512 may also be placed in contactwith the vessel wall 504. While FIG. 7 illustrates the sensingelectrodes 514, 516 in direct contact with the vessel wall, it iscontemplated that the sensing electrodes 514, 516 may be positioned awayfrom the vessel wall 504 in an off-the-wall configuration.

The ablation electrodes 512 and the sensing electrodes 514, 516 may beused to monitor the impedance of the local tissue. While not explicitlyshown, the ablation electrodes 512 and the sensing electrodes 514, 516may be connected through separate insulated conductors to a control unit(such as control unit 18 in FIG. 1). The sensing electrodes 514, 516 maybe spaced a distance from one another such that voltage applied to thesensing electrodes 514, 516 may cause current to flow between thesensing electrodes 514, 516 through the blood and nearby tissues.Measurement of the current may allow the resistance or complex impedanceof the blood and tissue to be calculated. Various frequencies may beused to determine one or more impedance values, or a simpler calculationof resistance at low frequency can be utilized.

In some instances, it may be desirable to calculate the impedance of theblood or other fluid within the body lumen 502. The modulation systemmay include a catheter shaft 518 including a lumen for perfusing saline520 or other fluid with known conductivity into the body lumen 502. Insome instances, the perfused fluid 520 may be provided at roomtemperature or cooler. It is contemplated that multiple fluids and/orconcentrations with known conductivity may be used. The impedance may bedetermined while the fluid 520 is being perfused. The difference betweenthe impedance calculated with blood and the impedance calculated withthe perfused fluid may be used to calculate the impedance of the blood.

While not explicitly shown, skin-contact ground pads may also beconnected through an electrical conductor to the control unit. Asvoltage is applied to the ablation electrodes 512, current may passthrough the local tissue and additional body tissue to the ground pads.Analysis of the impedance measurements between the ablation electrodes512 and the sensing electrodes 514, 516 and between the ablationelectrodes 512 and the ground pads and/or between the sensing electrodes514, 516 and the ground pads may determine the tissue impedance in thelocal tissue (e.g. target region) adjacent the electrodes 512, 514, 516.

Tissue impedance may be monitored during simultaneous RF ablation (e.g.energy is applied simultaneously to the ablation electrodes 512 and thesensing electrodes 514, 516) or during an ablation/sensing duty cyclewhich may be used alternate between ablation and impedance measurements.The tissue impedance may be determined in a similar manner to thatdiscussed with respect to other modulation systems described herein. Asablation of the target region progresses, the impedance properties ofthe local tissue may change thus changing the impedance calculatedbetween the ablation electrodes 512 and the contact ground pad and/orbetween the ablation electrodes 512 and the sensing electrodes 514, 516.Multiple measurements between the electrodes 512, 514, 516 and/or theground pads (with blood or perfused fluid 520) may account for thelocation of the system 500 and vessel geometry effects. It iscontemplated that poor ground pad contact may also be detected duringthe ablation process.

While not explicitly shown, the ablation electrodes 512 may be connectedto a control unit (such as control unit 18 in FIG. 1) by electricalconductors. Once the modulation system 500 has been advanced to thetreatment region, energy may be supplied to the ablation electrodes 512.The amount of energy delivered to the ablation electrodes 512 may bedetermined by the desired treatment as well as the feedback obtainedfrom the impedance calculations. It is contemplated that the impedanceof the blood, local tissue, and body tissue may be determined prior toand/or during the ablation procedure. Once the target tissue has begunto rise in temperature, and/or denature, the electrical properties ofthe tissue may begin to change. As the target tissue is ablated, thechange in impedance may be analyzed to determine how much tissue hasbeen ablated. The power level and duration of the ablation may beadjusted accordingly based on the impedance of the tissue. In someinstances, the modulation system 500 may monitor impedance values of thesurrounding tissue prior to beginning the ablation procedure and adjustthe ablation parameters accordingly. It is further contemplated thatother electrical properties of the local tissue such as permittivityand/or conductivity may be used to set the current and/or power for RFor other sources of ablation energy to target tissues.

The modulation system 500 may be advanced through the vasculature in anymanner known in the art such, but not limited to, those methodsdiscussed with respect to other modulation systems described herein.Once the ablation electrodes 512 of the modulation system 500 have beenplaced adjacent to the desired treatment area, positioning mechanismsmay be deployed, if so provided. For example, once the distal end region510 has been placed adjacent to the target region, the catheter shaft518 may be retracted and the framework 508 allowed to expand in similarmanners to those discussed with respect to modulation system 400.

As discussed above, the ablation electrodes 512 and the sensingelectrodes 514, 516 may be connected to a control unit (such as controlunit 18 in FIG. 1) by insulated electrical conductors. Once themodulation system 500 has been advanced to the treatment region, energymay be supplied to the ablation electrodes 512. As discussed above, theenergy may be supplied to both the ablation electrodes 512 and/or thesensing electrodes 514, 516 simultaneously or in an alternating dutycycle as desired. The amount of energy delivered to the ablationelectrodes 512 may be determined by the desired treatment as well as thefeedback provided by the sensing electrodes 514, 516. The modulationsystem 500 may be radially, longitudinally, and/or circumferentiallyrepositioned and energy subsequently applied as many times as necessaryto complete the desired ablation. The number of times the modulationsystem 500 is repositioned may be determined by the number and size ofthe ablation electrodes 512 on the elongate member 506.

Those skilled in the art will recognize that the present invention maybe manifested in a variety of forms other than the specific embodimentsdescribed and contemplated herein. Accordingly, departure in form anddetail may be made without departing from the scope and spirit of thepresent invention as described in the appended claims.

What is claimed is:
 1. A method for detecting tissue changes duringtissue modulation in a patient, the method comprising: inserting atissue modulation system into a lumen in the patient, the tissuemodulation system comprising: an elongate shaft having a proximal endregion and a distal end region; at least two electrodes disposedadjacent to the distal end region, a first electrode of the at least twoelectrodes spaced a distance from a second electrode of the at least twoelectrodes; advancing the tissue modulation system through the lumensuch that the distal end region is adjacent to a target region withinthe patient while the proximal end region remains outside the patient;applying a voltage to the modulation system to impart a current betweenthe first and second electrodes; calculating an impedance of the targetregion from the current; applying a voltage to at least one of the firstor second electrodes to effect tissue modulation on the target region;and monitoring the current between the first and second electrodes forchanges in the impedance of the target region.
 2. The method of claim 1,wherein the impedance of the target region is calculated beforeeffecting tissue modulation on the target region.
 3. The method of claim1, wherein monitoring the current between the first and secondelectrodes for changes in the impedance of the target region isperformed simultaneously with the tissue modulation.
 4. The method ofclaim 1 wherein monitoring the current between the first and secondelectrodes for changes in the impedance of the target region and thetissue modulation are performed alternately.
 5. The method of claim 1,wherein the amount of voltage applied to at least one of the first orsecond electrodes to effect tissue modulation on the target region isdetermined at least in part by the calculated impedance of the targetregion.
 6. The method of claim 1, further comprising withdrawing thetissue modulation system from the patient.
 7. The method of claim 1,wherein the tissue modulation includes ablation.
 8. A method fordetecting tissue changes during tissue ablation, the method comprising:advancing a tissue ablation system through a lumen such that a distalend region thereof is adjacent to a target region, the tissue ablationsystem comprising: an elongate shaft having a proximal end region and adistal end region; at least two electrodes disposed adjacent to thedistal end region, a first electrode of the at least two electrodesspaced a distance from a second electrode of the at least twoelectrodes; applying a voltage to the ablation system to impart acurrent between the first and second electrodes; calculating animpedance of the target region from the current; and applying a voltageto at least one of the first or second electrodes to effect tissueablation on the target region; and monitoring the current between thefirst and second electrodes for changes in the impedance of the targetregion.
 9. The method of claim 8, wherein the impedance of the targetregion is calculated before effecting tissue ablation on the targetregion.
 10. The method of claim 8, wherein monitoring the currentbetween the first and second electrodes for changes in the impedance ofthe target region is performed simultaneously with the tissue ablation.11. The method of claim 8 wherein monitoring the current between thefirst and second electrodes for changes in the impedance of the targetregion and the tissue ablation are performed alternately.
 12. The methodof claim 8, wherein the amount of voltage applied to at least one of thefirst or second electrodes to effect tissue ablation on the targetregion is determined at least in part by the calculated impedance of thetarget region.
 13. The method of claim 8, further comprising removingthe tissue ablation system from the lumen.
 14. The method of claim 8,wherein advancing the tissue ablation system through a lumen includespositioning the distal end region of the tissue ablation system adjacentthe target region within a patient while maintaining the proximal endregion of the elongate shaft outside the patient.